At High Altitude, Preeclampsia With Fetal Growth Restriction Can Exacerbate Fetal Hypoxia

NEW YORK (Reuters Health) – Preeclampsia complicated by fetal growth restriction (FGR) can augment fetal hypoxia at high altitude and increase the risk of neonatal pulmonary hypertension and pulmonary circulation abnormalities, according to new findings from Bolivia.

While the risk of pulmonary hypertension was increased in newborns, this was not the case later in infancy, however, researchers report in Hypertension.

“Our observations highlight important temporal windows for the prevention of pulmonary vascular disease among babies born to highland residents or those with exaggerated hypoxia in utero or newborn life,” Dr. Colleen G. Julian, of the University of Colorado School of Medicine, in Aurora, and colleagues write.

Half of Bolivia’s population lives above 3,000 meters (9,843 feet) of altitude, “where the proportion of pregnancies complicated by preeclampsia and FGR are 3-fold greater relative to low altitude even under comparable socioeconomic conditions,” the authors note.

Bolivia also has the highest under-5 mortality rate in Latin America, and one factor is “acute and subacute pulmonary vascular disease during infancy and childhood,” they add. Compared with their healthy counterparts, young adults in high-altitude Bolivia with elevated pulmonary-artery pressure are more likely to have been born to a mother with preeclampsia or have experienced perinatal hypoxia.

To explore whether preeclampsia with or without FGR exaggerated fetal hypoxia and impaired angiogenesis in the fetal lung, leading to circulatory abnormalities, Dr. Julian and her colleagues recruited 79 mother-child pairs (39 mothers with preeclampsia and 40 without) in Bolivia. All children were delivered by unlabored cesarean section at a large maternal-infant hospital in the La Paz/El Alto metro area, which is at an altitude of 3,600 to 4,100 meters.

On average, infants of preeclamptic mothers were born 2.7 weeks earlier and weighed 494 g less than controls after adjustment for gestational age. These infants also were three times more likely to be premature, seven times more likely to be born with FGR, nearly eight times more likely to be transferred to a neonatal intensive-care unit and more frequently received oxygen therapy.

“Preeclampsia augmented fetal hypoxia and increased the risk of (pulmonary hypertension) in the neonate but not later in infancy. Pulmonary abnormalities were confined to preeclampsia cases with fetal growth restriction,” the researchers report.

Maternal and cord blood levels of the anti-angiogenic factor sFlt1 (soluble fms-like tyrosine kinase) were higher in preeclampsia than in controls. Even after accounting for the independent effects of FGR and gestational age at birth, these elevated sFlt1 concentrations were positively associated with indirect indices of systolic pulmonary-artery pressure in the offspring.

The authors note that “the pulmonary vascular abnormalities we observed in neonates born to preeclampsia cases normalized during infancy.” They say this is consistent with other research, which however also indicates that “infants experiencing early pulmonary vascular insults are at an increased risk of progressive pulmonary vascular abnormalities in later life.”

Dr. Roberta L. Keller, professor of clinical pediatrics at the University of California, San Francisco, told Reuters Health by email that regardless of whether the most-affected infants are exposed to preeclampsia and then develop FGR, or are exposed additionally to maternal hypoxia, “these infants then live at the altitude they were exposed to in utero and are continuing to be exposed to hypoxia.”

This in turn “may increase their chance of abnormal vascular growth and development,” said Dr. Keller, who was not involved in the study.

Dr. Philip Levy, assistant professor of pediatrics at Boston Children’s Hospital, who also was not part of the study, told Reuters Health by email that it “highlights the realization that multiple insults (preeclampsia, fetal growth restriction, and prematurity) will increase the susceptibility for future insults that will eventually unlock/unmask clinical symptoms.”

Dr. Julian did not reply to a request for comments.

SOURCE: Hypertension, online April 19, 2022.

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